Bristol buys into AI-designed immune drug from Exscientia

 Bristol Myers Squibb has exercised an option on an immune-modulating drug candidate developed by UK artificial intelligence specialist Exscientia, paying $20 million for the buy-in as part of their $1.2 billion alliance.

The unnamed drug candidate acts on an immunological kinase enzyme, which has proven hard to target using conventional drug discovery techniques because challenges relating to “potency, selectivity, and overall drug-like properties,” according to the partners.

It’s the first candidate in a two-year-old collaboration between Exscientia and BMS’ Celgene unit focusing on oncology and immunology drug discovery – which was expanded in May with a $50 million upfront fee – to reach this milestone.

The candidate was selected within 11 months of beginning drug design, said Exscientia chief executive Andrew Hopkins.

The Oxford-based company is also in line for potential development milestone payments, as well as tiered royalty payments on product sales, with BMS overseeing the candidate’s clinical and commercial development.

Exscientia’s pipeline has been growing quickly on the back of a string of alliances with pharma partners, with three candidates now in clinical testing, and the company recently raised an impressive $225 million in fourth-round financing – led by SoftBank – that could swell to $525 million if it chooses.

The cash injection and BMS alliance have made Exscientia one of the most well-funded biotechs in the AI category and allowed it to bulk up its capabilities with the acquisition of Austrian rival Allcyte for $61 million in June.

Last year, the company claimed a milestone by starting the first-ever clinical trial of an AI-discovered drug therapy when partner Sumitomo Dainippon Pharma (DSP) started studies of DSP-1181 for obsessive-compulsive disorder.

That was followed by the start of trials for a cancer immunotherapy called EXS21546 that grew out of a collaboration with Evotec, and human testing of a second DSP project – DSP-0038 for psychosis associated with Alzheimer’s – in May.

The latest announcement deepens the partnership with BMS, and a is “further endorsement for the company’s AI-driven platform in discovering novel drug candidates,” said a spokesperson for Exscientia.

https://pharmaphorum.com/news/exscientia/

Verily scoops up a fellow software maker as Amy Abernethy scales its clinical trials platform

 Amy Abernethy now has a whole new set of tools to tap into as she scales up the clinical trial management platform at Verily.

The life sciences outfit — now officially a subsidiary of Alphabet on equal footing with Google — has acquired SignalPath for an undisclosed amount, giving it access to a system of digital solutions that make it easier to run clinical trials, and promise to simultaneously boost quality and efficiency.

“It’s our goal to modernize the way clinical trials are conducted for patients, researchers and sponsors alike,” said Abernethy, who left a top leadership position at the FDA to become Verily’s president of clinical studies platforms.

Verily has built a clinical trial system and evidence generation platform it calls Baseline, which offers data aggregation and analytics tools, as well as data collection options (think sensors and biomarkers) designed with decentralized and hybrid trials in mind. As part of that effort, it’s gathered a community of 500,000 people who have expressed interest in joining clinical trials promoted on Baseline.

With a similar goal, SignalPath was founded in 2014 to develop and sell a cloud-based portfolio to anyone who’s tasked with managing a clinical trial. Although no dollar figure was tied to the deal, Verily says it marks its first major acquisition.

The team will stay in Raleigh, NC even as they become Verily employees.

SignalPath CEO Brad Hirsch said integrating its suite of software within Verily’s business “accelerates our ability to scale these solutions and make them available to a larger group of sites as well as provide entirely new opportunities to our network.”

The acquisition comes as the FDA recently shot down an attempt by Verily to add a virtual motor exam for Parkinson’s disease with the Google smartwatch. In its rejection letter, the FDA said the motor exam and Verily’s algorithm, which sought to assess the motor symptom severity in adults who have been diagnosed with the debilitating disease, are “limited in their capacity to evaluate meaningful aspects of concepts of interest that are relevant to the patients’ ability to function in day-to-day life.”

https://endpts.com/verily-scoops-up-a-fellow-software-maker-as-amy-abernethy-scales-its-clinical-trials-platform/

Israel finds COVID-19 vaccine booster significantly lowers infection risk

 A third dose of Pfizer's COVID-19 vaccine has significantly improved protection from infection and serious illness among people aged 60 and older in Israel compared with those who received two shots, findings published by the Health Ministry showed on Sunday.

The data were presented at a meeting of a ministry panel of vaccination experts on Thursday and uploaded to its website on Sunday, though the full details of the study were not released.

The findings were on par with separate statistics reported last week by Israel's Maccabi healthcare provider, one of several organisations administering booster shots to try to curb the Delta coronavirus variant.

Breaking down statistics from Israel's Gertner Institute and KI Institute, ministry officials said that among people aged 60 and over, the protection against infection provided from 10 days after a third dose was four times higher than after two doses.

A third jab for over 60-year-olds offered five to six times greater protection after 10 days with regard to serious illness and hospitalisation.

That age group is particularly vulnerable to COVID-19 and in Israel was the first to be inoculated when the vaccine drive began in late December.

In recent weeks, the health ministry has said immunity has diminished over time for seniors and younger people as well. Most vaccinated people who fell severely ill in Israel were over 60 and with underlying health conditions.

Israel started administering third jabs to over 60-year-olds on July 30. On Thursday it dropped the age of eligibility for a booster to 40, and included pregnant women, teachers and health care workers below that age. Third doses are given only to those who received their second shot at least five months ago.

The United States has announced plans to offer booster shots to all Americans, citing data showing diminishing protection. Canada, France and Germany have announced booster campaigns.

Fighting an outbreak of the Delta variant since June, Israel presently has one of the world's highest infection rates per capita. Close to 1.5 million people out of the country's 9.3 million population have taken a third jab.

https://news.yahoo.com/israel-finds-covid-19-vaccine-185537259.html

Aduhelm Approval Could Imperil Woodcock's Future as FDA Commissioner

 Since the beginning of President Joe Biden's administration, Janet Woodcock, the longtime director of the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA), has served as acting commissioner. But a controversial approval of an Alzheimer’s medication could prevent her from dropping the “acting” from her title.

According to Bloomberg, Woodcock faces heavy opposition from an evenly divided U.S. Senate, particularly from West Virginia Sen. Joe Manchin, who has been critical of the approval process for Biogen’s Aduhelm, formerly known as aducanumab.

Aduhelm was approved by the FDA in June under accelerated approval. But the approval was highly controversial due to an overwhelming rejection of the medication by the agency’s advisory committee. Following the FDA decision to approve the medication, at least three members of that advisory committee resigned in protest.

Public Citizen, a watchdog group, called for additional resignations at the FDA, including Woodcock’s, due to what that group said is a lack of clinical data supporting approval. A U.S. House of Representatives committee has planned to investigate the approval process, as well as the pricing of the drug, which has a list price of $56,000 per year.

Manchin has been critical of the approval of Aduhelm and of Woodcock. Bloomberg cited a letter Manchin sent to the White House in June following the approval of Aduhelm, calling for a replacement to Woodcock. He argued that not having a commissioner in place impacts the response to the pandemic, as well as other regulatory concerns.

According to Bloomberg, Manchin wrote, “Without a permanent, confirmed commissioner in place to lead the FDA, important decisions that impact the country’s response to Covid-19 will be slowed and prevent additional work to combat the ongoing drug overdose epidemic.”

Woodcock, 72, first joined the FDA in 1986 and has served in CDER since 1994 in a variety of leadership roles. Like many in leadership in the FDA, Woodcock has shifted her focus from regulatory approvals to the ongoing COVID-19 crisis. In May 2020, she temporarily stepped away from her CDER duties to assist Operation Warp Speed, the pandemic response under the previous administration, and the federal government’s efforts to rapidly develop vaccines against the novel coronavirus.

Despite the mounting criticism, Biden has not indicated when he will announced a permanent commissioner. Under federal rules, Woodcock is able to serve as acting FDA commissioner until Nov. 15, unless the president nominates someone during that time who has yet to be confirmed by the Senate.

The White House, which is still managing the ongoing COVID-19 crisis amidst a resurgence of spread due to the Delta variant, has not publicly tipped its hand regarding a permanent commissioner. A spokesperson for the White House told Bloomberg that the FDA currently has “strong acting leadership in place” while the government responds to the pandemic. Spokesman Chris Meagher said the administration will share information regarding a nominee “with the requisite expertise and leadership for this job.”

https://www.biospace.com/article/woodcock-s-future-as-acting-fda-commissioner-in-jeopardy-due-to-political-opposition/

Cognitive rehabilitation improves cognitive impairment in MS

 In a review of recent literature, a team of researchers from Kessler Foundation conclude that cognitive rehabilitation programs are efficacious in treating multiple sclerosis-related cognitive dysfunction, and urge clinicians to consider this low-cost, low-risk, yet effective treatment approach for their patients.

The article, "Neurological update: cognitive rehabilitation in multiple sclerosis" was published in Journal of Neurology on May 24, 2021. The authors are Michelle H. Chen, PhD, Nancy D. Chiaravalloti, PhD, and John DeLuca, PhD, of Kessler Foundation. The authors have academic appointments at Rutgers New Jersey Medical School.

Cognitive impairment is a common and debilitating symptom of multiple sclerosis (MS), affecting as many as two-thirds of people with the disease. Symptoms of cognitive impairment vary among individuals, but often include slow information processing speed and inefficient learning and memory. Such deficits can be extremely disruptive to everyday life, affecting a person's ability to manage their disease, complete commonplace errands, and maintain employment. Unfortunately, there is no gold-standard treatment for MS-related cognitive impairment, as medications approved to treat MS have shown limited efficacy in treating cognitive dysfunction.

One promising treatment approach is cognitive rehabilitation, in which behavioral interventions are used to improve cognition. There are two general approaches to cognitive rehabilitation: restorative and compensatory. Restorative cognitive rehabilitation (also known as cognitive remediation) aims to reinforce, strengthen, and recover cognitive skills, typically through repetitive cognitive exercises using computer-assisted paradigms. In contrast, compensatory cognitive rehabilitation does not aim to restore lost cognitive skills. Rather, it helps patients compensate for their cognitive difficulties using various strategies such as visualization and reminders.

In their review, the Kessler team summarized the current state of cognitive rehabilitation research, both restorative and compensatory, among people with MS. Based on available evidence, they suggest that cognitive rehabilitation is an effective approach to improving MS-related cognitive impairment, as demonstrated by 81 published studies, most of which were published since 2011.

"Cognitive rehabilitation should be part of a comprehensive treatment plan for people with MS who experience cognitive deficits," said co-author Dr. DeLuca, Senior Vice President for Research and Training at Kessler Foundation. "Given the lack of approved pharmacological treatments, behavioral approaches are the best treatment options that clinicians can currently offer," he stressed. "Patients generally report enjoying treatment, which would be conducive to compliance. Furthermore, computer-based treatments can be easily delivered at home, making this low-cost effective intervention more convenient and accessible to individuals in need."

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Story Source:

Materials provided by Kessler Foundation. Note: Content may be edited for style and length.

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Journal Reference:

1. Michelle H. Chen, Nancy D. Chiaravalloti, John DeLuca. Neurological update: cognitive rehabilitation in multiple sclerosis. Journal of Neurology, 2021; DOI: 10.1007/s00415-021-10618-2

https://www.sciencedaily.com/releases/2021/08/210819195038.htm

Covid-19 vaccine by Arcturus, Singapore's Duke-NUS in phase 2 trials

 Three different Covid-19 messenger RNA vaccines which may have reduced side effects when administered are being developed with Singapore's involvement in their clinical trials.

Developed by United States-firm Arcturus Therapeutics, the three vaccine candidates can be given at a much lower dose than the mRNA vaccines now available - such as those by Pfizer and Moderna - because of the "self-amplifying" mRNA technology they use.

Each dose of the Arcturus vaccine contains five micrograms of vaccine, compared to 30 mcg in the Pfizer vaccine and 100 mcg in the Moderna vaccine.

The first vaccine, known as ARCT-021, targets the wildtype, or original Sars-CoV-2 virus, and was developed together with the Duke-NUS Medical School in Singapore. Local phase two trials, administered by SingHealth's Investigational Medicine Unit, are still ongoing.

The two newer vaccines - ARCT-154 and ARCT-165 - target the four variants of concern, Alpha, Beta, Gamma and Delta.

The local clinical trials will evaluate the vaccines' safety and immune response against the variants, and as possible booster shots for people who have received the Pfizer vaccines, said Associate Professor Jenny Low, the unit's deputy clinical and scientific director.

Arcturus' chief executive Joseph Payne told The Straits Times that while both vaccines have shown effectiveness against the variants when tested on primates, the ARCT-154 showed a stronger response to the Delta variant, while the ARCT-165 had a bias for the Beta variant.

The ARCT-154 vaccine is also undergoing clinical trials in Vietnam, in parallel with the trials conducted here. The trials here will also evaluate the vaccine as a booster jab. The data for both trials will be pooled in November, he added.

While conventional mRNA vaccines "teach" the cells to produce the Sars-CoV-2 viral spike protein to trigger an immune response in the body, the self-amplifying mRNA vaccine produces the protein at a lower level for a longer period of time - usually a couple of weeks, said Mr Payne.

The longer duration will generate the same neutralising antibody response in the body as well as help it develop a more robust T-cell response. T-cells are thought to confer long-lasting immunity to the virus and its variants.

In addition, having a lower dose also means that each dose carries fewer lipid nanoparticles that deliver the mRNA and an ingredient known as polyethylene glycol (PEG), which could sometimes trigger a rare allergic reaction known as anaphylaxis. This could potentially improve the vaccine's safety profile, he added.

Asked if the lower vaccine dose would mean a lower chance or incidence rate of myocarditis (heart inflammation), Mr Payne said this was a possibility.

But while myocarditis has not been seen in trials for Arcturus' vaccines so far, more robust data is needed, he said.

https://www.straitstimes.com/singapore/clinical-trials-ongoing-for-arcturus-covid-19-vaccines-which-may-have-fewer-side-effects

Facebook: Post casting doubt on covid vaccine was most popular on site Jan.-Mar.

 Facebook said Saturday evening that an article raising concerns that the coronavirus vaccine could lead to death was the top performing link in the United States on its platform from January through March of this year, acknowledging the widespread reach of such material for the first time.

It also said another site that pushed covid-19 misinformation was also among the top 20 most visited pages on the platform.

Facebook earlier this year faced a torrent of criticism from President Biden and others who have alleged that the company has allowed misinformation about coronavirus vaccines to flourish. White House officials have alleged that many Americans are reluctant to take the coronavirus vaccine, in part, because of false or misleading information they have read on social media services, including Facebook.

In releasing a report that the company had previously shelved, Facebook attempted to push back against critics, arguing that the definition of health misinformation is often less black and white than what some would make it seem.

For example, the article that surged earlier this year on Facebook’s platform, which is used by more than 2.8 billion people each month, was a factual article from The South Florida Sun Sentinel (distributed by the Chicago Tribune) about the Centers for Disease Control and Prevention investigating the death of a doctor who passed away two weeks after taking the coronavirus vaccine, according to the report (Months later, the medical examiner’s office found that there wasn’t enough evidence to say whether the vaccine played a role in the doctor’s death).

Facebook has said it will take down outright false information about covid-19, but has argued that conversations about factual articles should not be suppressed.

In a report published this past week, Facebook had identified the most popular information shared on its platform from April to June, a disclosure that raised questions about why the company was not revealing popular posts from the earlier part of this year.

The new release of the January through March data by Facebook came one day after the New York Times first reported that it had been withheld by senior executives. The disclosure reflects the challenge of being open with the public at a time when the social network is being attacked by the White House as well as experts for fomenting the spread of health misinformation. Previously, the company had only shared how much covid-related misinformation it has removed, and has been careful not to acknowledge up to this point what role they’ve played in disseminating material that mislead the public about the virus and the vaccine.

For months, executives have debated releasing both this report and other information, according to a person familiar with the company’s thinking. In those debates, the conversations revolved around whether releasing certain data points were likely to help or hurt the company’s already-battered public image. In numerous instances, the company held back on investigating information that appeared negative, the person said.

In July, President Biden accused platforms like Facebook of “killing people” for spreading misinformation about covid-19, while the Surgeon General called such misinformation an “urgent threat.” (Biden subsequently walked back the comment).

After Biden’s comment, there was fear inside Facebook that the narrative was getting out of control, the person said. Facebook had been in discussions for months with the White House and the U.S. Surgeon General. Biden administration officials had repeatedly asked for data about the extent of misinformation on the company’s platform, according to three additional people familiar with the discussions who spoke on the condition of anonymity to discuss private matters.

At first, Facebook only wanted to share data that cast the company in a positive light, including promoting its research that the company has taken down 20 million pieces of content containing misinformation about covid-19.

But as the White House pushed further, Facebook planned to release a transparency report that would show the 100 pieces of most popular content on the platform.

The problem was that they feared what they might find. They were also cautious because they felt that the narrative about what misinformation is was often misconstrued.

As product managers, engineers, policy officials, and other executives began to dig into the data, they found that in the first quarter of this year, one of the most popular pages on the network was a page run by the Epoch Times, a right-wing anti-China publication that has promoted the violent QAnon conspiracy theories and misleading claims of voter fraud related to the 2020 election.

Another one of the most popular articles was the Sun Sentinel piece. The article was promoted on Facebook by several anti-vaccine groups.

In a statement, Facebook spokesman Andy Stone said it had “considered making the report public earlier but since we knew the attention it would garner, exactly as we saw this week, there were fixes to the system we wanted to make.” He declined to elaborate on the fixes, except to say that one item involved fixing a technical bug.

In tweets posted on Saturday evening, Stone said that “given the interest in the first version we did not release, we’ve decided just to make it public. It’s not gleaming, but we’re trying to make progress.”

He said that the case of the Sun Sentinel article “does illustrate just how difficult it is to define misinformation.”

Facebook’s leadership has long felt that skepticism about any subject, including vaccines, should not be censored in a society that allows robust public debate. The company has also viewed research which shows that people are most likely to have their minds changed by people who they trust, including friends, family, and people in their social network. The company, along with other experts, argue that is a strong reason to allow material that may raise questions to be posted and discussed on the platform.

The challenge is that certain factual stories that might cast doubt on vaccines are often promoted and skewed by people and groups that are opposed to them. The result is that factual information can become part of an ideological campaign. Facebook has been slow to remove or block some of the leading anti-vaccine figures that spread such ideas.

In releasing the report, its authors noted that the most popular content still represented just 0.05% of all content views by U.S. users in the first quarter.

Other top links came from Unicef, ABC News, and The Washington Post.

https://www.washingtonpost.com/technology/2021/08/21/facebook-coronavirus-vaccine/